柔性纳米脂质体构建肺部靶向给药系统的研究

Study on the Application of Flexible Nano-Liposomes in the Construction of Pulmonary Targeted Drug Delivery System

目的研究以胶体为核心的柔性纳米脂质体(flexible nano-liposomes,FNLs)包载蛋白类药物在肺部靶向递药的有效性和安全性。方法应用注入法结合W/W乳化法制备FNLs,并通过制剂学方法检测FNLs的理化性质。通过肺部滴注insulin-FNLs,检测相应血糖值;将异硫氰酸荧光素经肺部滴注给药,评估FNLs经肺转运进入体循环后药物在肺泡的沉积情况;通过对肺组织进行苏木素-伊红染色,初步评价FNLs经肺部给药的安全性。结果 FNLs形态圆整,表面光滑,粒径为(153±0.94)nm,Zeta电位为-(20.9±0.21)m V;FNLs能增强降血糖效果,提高相对生物利用度,最低血糖值百分比可以达到(18.25±4.19)%。FNLs能延长药物在肺内的滞留时间,在肺部具有较好的耐受性。结论 FNLs作为肺部靶向递药载体,经肺部给药可以克服蛋白类药物肺内吸收屏障,增加生物利用度,为新型肺内给药系统的研发奠定基础。

OBJECTIVE To study on the effectiveness and safety of the colloid-core flexible nano-liposomes（FNLs） mediated protein drugs by pulmonary drug delivery. METHODS FNLs were prepared by the injection method combined with emulsion technology, physiochemical properties of FNLs were detected by the method of preparation. Intratracheal instillation of insulin-FNLs was performed to evaluated hypoglycemic effect. FITC administered in accordance with the intratracheal instillation into the lungs, to estimate the FITC-FNLs deposition ratio. Histological changes in the lung were also observed to evaluate the safety of FNLs by hematoxylin and eosin. RESULTS FNLs showed satisfied elliptic morphology, with average particle size（153±0.94）nm, Zeta potential-（20.9±0.21）m V. FNLs promoted insulin pulmonary absorption effectively and showed good relative pharmacological bioavailability, to achieve a significant hypoglycemic effect, the minimum reductions of the blood glucose concentration reached（18.25±4.19）%; FNLs could be increased drug deposition in the lungs to promote drug into the systemic circulation, and better tolerance in the lungs. CONCLUSION FNLs as pulmonary drug delivery system, can be overcome intrapulmonary absorption barrier by the pulmonary administration of protein drugs, increased bioavailability, lay the foundation for development of pulmonary drug delivery system.